Skip to main content
main-content

23.01.2018 | Original Article | Ausgabe 3/2018

Metabolic Brain Disease 3/2018

Neonatal mitochondrial leukoencephalopathy with brain and spinal involvement and high lactate: expanding the phenotype of ISCA2 gene mutations

Zeitschrift:
Metabolic Brain Disease > Ausgabe 3/2018
Autoren:
Irene Toldo, Margherita Nosadini, Chiara Boscardin, Giacomo Talenti, Renzo Manara, Eleonora Lamantea, Andrea Legati, Daniele Ghezzi, Giorgio Perilongo, Stefano Sartori
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s11011-017-0181-3) contains supplementary material, which is available to authorized users.

Highlights

-this is the second report associating ISCA2 gene mutation to a human disease;
-ISCA2 gene mutations cause a neonatal neurodegenerative mitochondrial leukoencephalopathy;
-this condition presents some overlapping features with early-onset LBSL;
-the phenotype of our case is unique and different to that of the other 6 reported ISCA2-mutated cases.
A comment to this article is available online at https://​doi.​org/​10.​1007/​s11011-018-0253-z.

Abstract

A homoallelic missense founder mutation of the iron-sulfur cluster assembly 2 (ISCA2) gene has been recently reported in six cases affected by an autosomal recessive infantile neurodegenerative mitochondrial disorder. We documented a case of a 2-month-old girl presenting with severe hypotonia and nystagmus, who rapidly deteriorated and died at the age of three months. Increased cerebral spinal fluid level of lactate, documented also at the brain spectroscopy, involvement of the cortex, restricted diffusion of white and gray matter abnormalities, sparing of the corpus callosum and extensive involvement of the spinal cord were observed. Her clinical presenting features and course as well as some neuroradiological findings mimicked those of early-onset leukoencephalopathy with brainstem and spinal cord involvement and high brain lactate (LBSL). The analysis of the mitochondrial respiratory chain function showed a reduced activity of complexes II and IV. The girl harboured two heterozygous mutations in the ISCA2 gene. A comprehensive review of the literature and a comparison with the cases of early onset LBSL enabled us to highlight significant differences in the clinical, biochemical and neuroradiological phenotype between the two conditions, which also emerged from the comparison with the other 6 reported cases of ISCA2 gene mutation previously reported. In summary, this represents the second report ever published associating ISCA2 gene mutation with a mitochondrial leukoencephalopathy, with a different genetic mechanism to the previous cases. Molecular analysis of ISCA2 should be included in the genetic panel for the diagnosis of early onset mitochondrial leukoencephalopathies.

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

★ PREMIUM-INHALT
e.Med Interdisziplinär

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de.

Weitere Produktempfehlungen anzeigen
Zusatzmaterial
Nur für berechtigte Nutzer zugänglich
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 3/2018

Metabolic Brain Disease 3/2018 Zur Ausgabe
  1. Sie können e.Med Neurologie & Psychiatrie 14 Tage kostenlos testen (keine Print-Zeitschrift enthalten). Der Test läuft automatisch und formlos aus. Es kann nur einmal getestet werden.

  2. Sie können e.Med Neurologie 14 Tage kostenlos testen (keine Print-Zeitschrift enthalten). Der Test läuft automatisch und formlos aus. Es kann nur einmal getestet werden.

  3. Sie können e.Med Psychiatrie 14 Tage kostenlos testen (keine Print-Zeitschrift enthalten). Der Test läuft automatisch und formlos aus. Es kann nur einmal getestet werden.

Neu in den Fachgebieten Neurologie und Psychiatrie